雌激素对小鼠肝脏纤维化的保护作用

Protective effect of estrogen on hepatic fibrosis in mice

目的探讨雌激素对小鼠肝脏纤维化的保护作用。方法 SPF级雄性C57BL/6J小鼠15只随机均分为三组:橄榄油组(Oil组),四氯化碳(CCl4)处理组(CCl4组),CCl4处理加雌激素1mg/kg干预组(CCl4+E组)。1周后用ELISA法检测血清ALT水平;HE染色、马松三色法和猩红染色法检测肝脏纤维化程度;Western blot检测肝脏组织Ⅰ型胶原蛋白表达,qRT-PCR检测Ⅰ型胶原α1链(Col1α1)、Ⅰ型胶原α2链(Col1α2)和α-平滑肌肌动蛋白(α-SMA)基因表达和免疫荧光染色检测α-SMA荧光表达强度。结果与CCl4组比较,CCl4+E组能降低小鼠ALT水平(P<0.05),CCl4+E组肝脏Col1α1、Col1α2和α-SMA的基因表达均较CCl4组降低(均P<0.05)。在肝星状细胞(HSC)-T6细胞系中,胶原基因启动子转录活性增加,雌激素能剂量依懒性下调胶原基因启动子的激活能力(P<0.05)。结论雌激素对CCl4诱导的小鼠肝脏纤维化具有保护作用,主要是通过抑制HSC细胞活化、降低细胞外基质的合成延缓肝纤维化进程。

Objective To investigate the protective effect of estrogen on hepatic fibrosis in mice .Methods Fifteen mice were equally assigned into three groups .Group A was treated with olive oil as blank control .Mice models of hepatic fibrosis in groups of B and C were established by subcutaneous injection of 25% carbon tetrachloride （CCl4 ） .The mice in group C were treated with estrogen 1 mg/kg for 48 hours .The mice were sacrificed one week after the injection .Serum levels of alanine aminotransferase （ALT ） was evaluated by ELISA .Hematoxylin ,eosin staining and Masson trichrome staining of liver tissues were performed for histopathological evaluation of liver fibrosis .The mRNA expressions of α‐SMA ,Col1α1 and Col1α2 and type Ⅰ collagen expression were assayed by qRT‐PCR and intensity of α‐SMA was detected by immunofluorescent staining ,respectively . Results Compared with group B ,ALT in group C was decreased （ P〈0 .05 ） and the mRNA expressions of a‐SMA ,Col1α1 and Col1α2 in group C were significantly inhibited in a dose‐dependent manner（P〈0 .05） .Conclusion Estrogen has a protective effect against CCl4‐induced liver fibrosis in mice by inhibiting hepatic stellate cells activation ,decreasing extracellular matrix synthesis and attenuating the process of liver fibrosis .